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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:KDM5B-PPP1R12B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM5B-PPP1R12B
FusionPDB ID: 41865
FusionGDB2.0 ID: 41865
HgeneTgene
Gene symbol

KDM5B

PPP1R12B

Gene ID

10765

4660

Gene namelysine demethylase 5Bprotein phosphatase 1 regulatory subunit 12B
SynonymsCT31|JARID1B|MRT65|PLU-1|PLU1|PPP1R98|PUT1|RBBP2H1A|RBP2-H1MYPT2|PP1bp55
Cytomap

1q32.1

1q32.1

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 5Bcancer/testis antigen 31histone demethylase JARID1Bjumonji, AT rich interactive domain 1Bjumonji/ARID domain-containing protein 1Blysine (K)-specific demethylase 5Bprotein phosphatase 1, regulatory subunit 98putative Dprotein phosphatase 1 regulatory subunit 12Bmyosin phosphatase target subunit 2myosin phosphatase-targeting subunit 2protein phosphatase 1, regulatory (inhibitor) subunit 12B
Modification date2020032020200313
UniProtAcc

Q9UGL1

Main function of 5'-partner protein: FUNCTION: Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as a tumor suppressor for melanoma. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity). {ECO:0000250|UniProtKB:Q80Y84, ECO:0000269|PubMed:12657635, ECO:0000269|PubMed:16645588, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17363312, ECO:0000269|PubMed:24952722, ECO:0000269|PubMed:26645689, ECO:0000269|PubMed:26741168, ECO:0000269|PubMed:27214403, ECO:0000269|PubMed:28262558}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000367264, ENST00000367265, 
ENST00000456180, 
ENST00000290419, 
ENST00000367270, ENST00000391959, 
ENST00000356764, ENST00000480184, 
ENST00000336894, ENST00000608999, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 13 X 9=163814 X 15 X 6=1260
# samples 1716
** MAII scorelog2(17/1638*10)=-3.26832870550331
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1260*10)=-2.97727992349992
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KDM5B [Title/Abstract] AND PPP1R12B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM5B [Title/Abstract] AND PPP1R12B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM5B(202742246)-PPP1R12B(202536906), # samples:2
Anticipated loss of major functional domain due to fusion event.KDM5B-PPP1R12B seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
KDM5B-PPP1R12B seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
KDM5B-PPP1R12B seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
KDM5B-PPP1R12B seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneKDM5B

GO:0034720

histone H3-K4 demethylation

20228790



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:202742246/chr1:202536906)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across KDM5B (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across PPP1R12B (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000367265KDM5Bchr1202742246-ENST00000608999PPP1R12Bchr1202536906+1407917419341932332
ENST00000367265KDM5Bchr1202742246-ENST00000336894PPP1R12Bchr1202536906+994217419341932332
ENST00000367264KDM5Bchr1202742246-ENST00000608999PPP1R12Bchr1202536906+13027689113880255
ENST00000367264KDM5Bchr1202742246-ENST00000336894PPP1R12Bchr1202536906+8890689113880255
ENST00000367265KDM5Bchr1202743740-ENST00000608999PPP1R12Bchr1202385914+16374157093442271097
ENST00000367265KDM5Bchr1202743740-ENST00000336894PPP1R12Bchr1202385914+12237157093442271097
ENST00000367265KDM5Bchr1202743740-ENST00000480184PPP1R12Bchr1202385914+295515709342826630
ENST00000367265KDM5Bchr1202743740-ENST00000356764PPP1R12Bchr1202385914+284215709342439501
ENST00000367264KDM5Bchr1202743740-ENST00000608999PPP1R12Bchr1202385914+1532251811331751020
ENST00000367264KDM5Bchr1202743740-ENST00000336894PPP1R12Bchr1202385914+1118551811331751020
ENST00000367264KDM5Bchr1202743740-ENST00000480184PPP1R12Bchr1202385914+19035181131774553
ENST00000367264KDM5Bchr1202743740-ENST00000356764PPP1R12Bchr1202385914+17905181131387424
ENST00000367265KDM5Bchr1202743741-ENST00000608999PPP1R12Bchr1202385915+16374157093442271097
ENST00000367265KDM5Bchr1202743741-ENST00000336894PPP1R12Bchr1202385915+12237157093442271097
ENST00000367265KDM5Bchr1202743741-ENST00000480184PPP1R12Bchr1202385915+295515709342826630
ENST00000367265KDM5Bchr1202743741-ENST00000356764PPP1R12Bchr1202385915+284215709342439501
ENST00000367264KDM5Bchr1202743741-ENST00000608999PPP1R12Bchr1202385915+1532251811331751020
ENST00000367264KDM5Bchr1202743741-ENST00000336894PPP1R12Bchr1202385915+1118551811331751020
ENST00000367264KDM5Bchr1202743741-ENST00000480184PPP1R12Bchr1202385915+19035181131774553
ENST00000367264KDM5Bchr1202743741-ENST00000356764PPP1R12Bchr1202385915+17905181131387424

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000367265ENST00000608999KDM5Bchr1202742246-PPP1R12Bchr1202536906+0.0258010140.97419894
ENST00000367265ENST00000336894KDM5Bchr1202742246-PPP1R12Bchr1202536906+0.0169863780.98301363
ENST00000367264ENST00000608999KDM5Bchr1202742246-PPP1R12Bchr1202536906+0.0029097060.9970902
ENST00000367264ENST00000336894KDM5Bchr1202742246-PPP1R12Bchr1202536906+0.0022515730.99774843
ENST00000367265ENST00000608999KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0011916810.9988084
ENST00000367265ENST00000336894KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0009931510.9990069
ENST00000367265ENST00000480184KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0033930660.99660695
ENST00000367265ENST00000356764KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.002141050.99785894
ENST00000367264ENST00000608999KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.000533450.9994666
ENST00000367264ENST00000336894KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0004430360.99955696
ENST00000367264ENST00000480184KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0037251990.9962748
ENST00000367264ENST00000356764KDM5Bchr1202743740-PPP1R12Bchr1202385914+0.0014728180.99852717
ENST00000367265ENST00000608999KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0011916810.9988084
ENST00000367265ENST00000336894KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0009931510.9990069
ENST00000367265ENST00000480184KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0033930660.99660695
ENST00000367265ENST00000356764KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.002141050.99785894
ENST00000367264ENST00000608999KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.000533450.9994666
ENST00000367264ENST00000336894KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0004430360.99955696
ENST00000367264ENST00000480184KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0037251990.9962748
ENST00000367264ENST00000356764KDM5Bchr1202743741-PPP1R12Bchr1202385915+0.0014728180.99852717

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for KDM5B-PPP1R12B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM5Bchr1202742246PPP1R12Bchr12025369061741263HYERILNPYNLFLSGDSLRQKQEKTS
KDM5Bchr1202742246PPP1R12Bchr1202536906689186HYERILNPYNLFLSGDSLRQKQEKTS
KDM5Bchr1202743740PPP1R12Bchr12023859141570212VERKILDLFQLNKACIDENLDMVKFL
KDM5Bchr1202743740PPP1R12Bchr1202385914518135VERKILDLFQLNKACIDENLDMVKFL
KDM5Bchr1202743741PPP1R12Bchr12023859151570212VERKILDLFQLNKACIDENLDMVKFL
KDM5Bchr1202743741PPP1R12Bchr1202385915518135VERKILDLFQLNKACIDENLDMVKFL

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Potential FusionNeoAntigen Information of KDM5B-PPP1R12B in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
KDM5B-PPP1R12B_202742246_202536906.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
KDM5B-PPP1R12Bchr1202742246chr1202536906689HLA-B15:30NLFLSGDSL0.59410.7307918

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Potential FusionNeoAntigen Information of KDM5B-PPP1R12B in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of KDM5B-PPP1R12B

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
6332NPYNLFLSGDSLRQKDM5BPPP1R12Bchr1202742246chr1202536906689

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM5B-PPP1R12B

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN6332NPYNLFLSGDSLRQ-7.9962-8.1096
HLA-B14:023BVN6332NPYNLFLSGDSLRQ-5.70842-6.74372
HLA-B52:013W396332NPYNLFLSGDSLRQ-6.83737-6.95077
HLA-B52:013W396332NPYNLFLSGDSLRQ-4.4836-5.5189
HLA-A11:014UQ26332NPYNLFLSGDSLRQ-10.0067-10.1201
HLA-A11:014UQ26332NPYNLFLSGDSLRQ-9.03915-10.0745
HLA-A24:025HGA6332NPYNLFLSGDSLRQ-6.56204-6.67544
HLA-A24:025HGA6332NPYNLFLSGDSLRQ-5.42271-6.45801
HLA-B44:053DX86332NPYNLFLSGDSLRQ-7.85648-8.89178
HLA-B44:053DX86332NPYNLFLSGDSLRQ-5.3978-5.5112
HLA-A02:016TDR6332NPYNLFLSGDSLRQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KDM5B-PPP1R12B

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
KDM5B-PPP1R12Bchr1202742246chr1202536906918NLFLSGDSLGACAGCCTAAGGCAGAAACAAGAAAAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of KDM5B-PPP1R12B

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
SARCKDM5B-PPP1R12Bchr1202742246ENST00000367264chr1202536906ENST00000336894TCGA-DX-A8BV-01A

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Potential target of CAR-T therapy development for KDM5B-PPP1R12B

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to KDM5B-PPP1R12B

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to KDM5B-PPP1R12B

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource